Asthma is the most common chronic illness in developed countries. Despite advances in our understanding of its pathogenesis and therapy, the morbidity and mortality associated with asthma are increasing both in the United States and worldwide. Upper respiratory viral infections are a major cause of asthma exacerbations, accounting for 80 to 85 percent of asthma attacks in children and 40 percent in adults. While rhinovirus and respiratory syncytial virus are the most common precipitants, any virus capable of promoting an acute respiratory infection has the potential to exacerbate asthma. The mechanisms by which viruses induce the onset of asthma or increase its severity are poorly understood, vary among viruses, and are likely to involve multiple pathways. These include pathophysiologic changes in the respiratory epithelium and alterations in airway inflammation through the activation/recruitment of T lymphocytes with the subsequent release of proinflammatory cell mediators. In an OVA-induced murine model of allergic airway disease, we have observed an increase in lung eosinophils, Th2 cytokines, and mucus production, along with elevated serum IgE levels and hyperreactivity to methacholine challenge. Concomitant infection with murine cytomegalovirus (MCMV) an opportunistic respiratory pathogen, resulted in a decrease in lung eosinophils, altered lung Th1/Th2 cytokine expression, and enhanced mucus production in this model. Thus, concomitant infection with MCMV resulted in two distinct outcomes, attenuation of airway eosinophilia and enhanced mucus production, and both events appear to be influenced by the local cytokine environment. We hypothesize that the decrease in airway eosinophilia observed in MCMV/challenged mice is due to a shift in the balance of Th1/Th2 cytokines in the lung, resulting from induction of IL-12 and lL-18 by MCMV infected/activated alveolar macrophages. Furthermore, we hypothesize that enhanced mucus production is the result of the recruitment/proliferation of TCRgd cells, in response to MCMV infected respiratory epithelium, with the subsequent release of IL-l0.